Massive Apixaban Overdose Confirmed with Blood Concentrations and Managed Without Bleeding: A Single Case Report

Abstract

Background Acute overdoses of apixaban, and other direct oral anticoagulants are relatively uncommon. The number of direct oral anticoagulants prescriptions in the United States is increasing, however reports on patient outcomes after documented overdose are sparse. Case report A 76-year-old man with a past medical history of atrial fibrillation and taking apixaban 5 mg twice daily presented to the emergency department 10 hours after reportedly ingesting 60-70 of his pills. He was alert and had a normal physical examination. Blood tests demonstrated an INR of 12, platelets of 161 000 cells/mm3, hemoglobin 9.7 g/dL, and creatinine 1.81 mg/dL. He received 60 g of activated charcoal and 4 units of fresh frozen plasma prophylactically. Initial blood apixaban concentration was 4 000 ng/mL. Repeat blood apixaban concentrations were 3 000 ng/mL and 2 200 ng/mL at 7 and 14 hours, respectively (thrapeutic range 91-321 ng/mL for a 5 mg twice daily dose). The hybrid anti-factor Xa activity did not correlate with blood apixaban concentrations. Apixaban elimination followed first-order kinetics with an apparent elimination half-life of 14 hours in the presence of impaired renal function. He did not have any minor or major bleeding events.

Half-life of Apixaban During Massive Apixaban Overdose

“…5 Although the patient discussed in the case report recently published in the Journal of Pharmacy Practice took activated charcoal to treat the apixaban overdose, the elimination half-life was approximately 16.23 h, which is prolonged compared with the elimination half-life (11.7 ± 3.3 hours) of apixaban at therapeutic dose. 1,4 As the author of this case report commented, renal disease associated with elevated creatinine and decreased glomerular filtration rate, as observed in this case, may have contributed to this prolonged elimination half-life. 1…”

“…1,4 As the author of this case report commented, renal disease associated with elevated creatinine and decreased glomerular filtration rate, as observed in this case, may have contributed to this prolonged elimination half-life. 1…”

“…4 The peak plasma concentration of apixaban reported in this case study was approximately 31 times higher than the therapeutic plasma concentration of apixaban. 1,4 The half-life of apixaban at therapeutic dose was reported to be 11.7 ± 3.3 h. 4 The calculated half-life of apixaban in a patient with self-poisoning of apixaban (5 mg × 60 tablet = 300 mg), which is approximately .923 times the amount of apixaban (325 mg) taken by the patient discussed in this case report, was reported to be 10.8 h, which is within the range of the half-life of apixaban administered at therapeutic dose. 1,4,5 Furthermore, previous cases reported that time to maximum observed plasma concentration of apixaban was 17 h in patients with apixaban poisoning, compared with 4 h in patients with therapeutic dose of apixaban.…”

“…I read with interest the case report titled “Massive Apixaban Overdose Confirmed with Blood Concentrations and Managed Without Bleeding: A Single Case Report” recently published in Journal of Pharmacy Practice . 1 Direct oral anticoagulant apixaban is a highly selective inhibitor of factor Xa, which is involved in common pathways for intrinsic and extrinsic coagulation. 2 I would like to comment on the estimated half-life of apixaban in this case report.…”

“…1,4 The half-life of apixaban at therapeutic dose was reported to be 11.7 ± 3.3 h. 4 The calculated half-life of apixaban in a patient with self-poisoning of apixaban (5 mg × 60 tablet = 300 mg), which is approximately .923 times the amount of apixaban (325 mg) taken by the patient discussed in this case report, was reported to be 10.8 h, which is within the range of the half-life of apixaban administered at therapeutic dose. 1,4,5 Furthermore, previous cases reported that time to maximum observed plasma concentration of apixaban was 17 h in patients with apixaban poisoning, compared with 4 h in patients with therapeutic dose of apixaban. 4,5 Considering these results, a previous case report suggests that treatment with activated charcoal may be effective in apixaban removal because of the delayed absorption of apixaban from the gastrointestinal tract in patients with apixaban poisoning.…”